The long-term goal of the proposed research is to develop new methods for assessing risk of fracture and osteoporosis using measures of bone mass, bone structure, and clinical data. Specifically, we will develop computerized radiographic methods for quantifying bone structure (through radiographic texture analysis: "RTA") that may be used together with measures of bone mass and clinical data for use in quantitatively assessing bone strength. We believe that our methods have the potential to aid in the assessment of osteoporosis and that the use of both bone mass and bone structure information should improve the predictive value for assessing fracture risk over that obtainable with BMD alone. Our hypothesis is that RTA of the trabecular bone pattern in bone radiographs yields information on bone strength and risk of fracture and, thus, will be useful in the assessment of osteoporosis. The specific aims to be addressed by the research in the new funding period are: (1) Further development of RTA features for the assessment of bone structure and risk of fracture, (2) Development of appropriate computer/human interfaces in order to effectively and efficiently display and convey RTA results, (3) Pre-clinical evaluation of the efficacies of RTA in predicting risk of fracture on an actual clinical population, and (4) Pre-clinical evaluation of RTA as a means to assess response to therapy. The potential significance of this research project lies in the fact that if the detection of high-risk patients can be accomplished with a reliable,low- dose, economical system, then screening for osteoporosis could be implemented more broadly, thereby allowing earlier treatment and a reduction in the risk of fracture. In addition, such techniques are expected to be useful in the monitoring of therapy for osteoporosis. We expect that with this grant renewal, we will be able to complete the research with a focus on translation of the results into the clinical arena.